US4049806AExpiredUtility

Cephalosporin type antibacterials

66
Assignee: SYNTEX INCPriority: Aug 15, 1975Filed: Aug 15, 1975Granted: Sep 20, 1977
Est. expiryAug 15, 1995(expired)· nominal 20-yr term from priority
Inventors:Philip J. Beeby
A61P 31/04C07D 501/24
66
PatentIndex Score
8
Cited by
5
References
39
Claims

Abstract

3-[3-(1-Methyltetrazol-5-ylthio)-prop-1-(t)-enyl]-7β-(α-phenylacetamido)-ceph-3-em-4-carboxylic acid; 7β-(α-phenylacetamido)-3-[3-(1,2,4-triazol-5-ylthio)-prop-1-(t)-enyl]-ceph-3-em-4-carboxylic acid derivatives and salts thereof; and intermediates and processes for preparing such compounds. The compounds are useful as antibacterials and are active against a wide variety of gram positive and gram negative bacteria.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
       1. A compound selected from the group having the formula: ##STR23## wherein the propenyl double bond is trans; R 1  is 1-methyltetrazol-5-yl; or 1,2,4-triazol-5-yl; R 2  is hydrogen, diphenylmethyl, p-methoxybenzyl, p-nitrobenzyl, o-nitrobenzyl, benzyl, t-butyl, 2,2,2,-trichloroethyl, phenacyl or pivaloyloxymethyl; R 3  is hydrogen or a group having the formulas: ##STR24## wherein R 4  is hydrogen, hydroxy, sulfo or carboxy; X is hydrogen or hydroxy; and pharmaceutically acceptable salts of the above compounds wherein R 3  is other than H. 
     
     
       2. The compound of claim 1 wherein the said compound is selected from the group having the formula: ##STR25## wherein R 1  and R 2  are as defined in claim 1. 
     
     
       3. The compound of claim 2 wherein R 2  is diphenylmethyl. 
     
     
       4. The compound of claim 3 wherein R 2  is hydrogen. 
     
     
       5. The compound of claim 4 wherein R 1  is 1-methyl-tetrazol-5-yl. 
     
     
       6. The compound of claim 4 wherein R 1  is 1,2,4-triazol-5-yl. 
     
     
       7. The compound of claim 1 wherein said compound is selected from the group having the formula: ##STR26## wherein R 1 , R 2  and R 4  are as defined in claim 1, and pharmaceutically acceptable salts thereof. 
     
     
       8. The compound of claim 7 wherein R 2  is diphenylmethyl. 
     
     
       9. The compound of claim 7 wherein R 2  is hydrogen and pharmaceutically acceptable salts thereof. 
     
     
       10. The compound of claim 9 wherein R 1  is 1-methyltetrazol-5-yl. 
     
     
       11. The compound of claim 10 wherein said compound is a sodium salt. 
     
     
       12. The compound of claim 10 wherein said compound is selected from the group of 3-[3-(1-methyltetrazol-5-ylthio)-prop-1-(t)-enyl]-7β-phenylactamido-ceph-3-em-4 -carboxylic acid and pharmaceutically acceptable salts thereof. 
     
     
       13. The compound of claim 10 wherein said compound is selected from the group of 3-[3-(1 -methyltetrazol-5-ylthio)-prop-1-(t)-enyl]-7β-(α-hydroxy-.alpha.-phenylacetamido)-ceph-3-em-4-carboxylic acid and pharmaceutically acceptable salts thereof. 
     
     
       14. The compound of claim 10 wherein said compound is selected from the group of 3-[3-(1-methyltetrazol-5-ylthio)-prop-1-(t)-enyl]-7β-(α-phenyl-α-sulfoacetamido)-ceph-3-em-4-carboxylic acid and pharmaceutically acceptable salts thereof. 
     
     
       15. The compound of claim 10 wherein said compound is selected from the group of 3-[3-(1-methyltetrazol-5-ylthio)prop-1-(t)-enyl]-7β-(α-carboxy-α-phenylacetamido)-ceph-3-em-4-carboxylic acid and pharmaceutically acceptable salts thereof. 
     
     
       16. The compound of claim 9 wherein R 1  is 1,2,4-triazol-5-yl. 
     
     
       17. The compound of claim 16 wherein said compound is a sodium salt. 
     
     
       18. The compound of claim 16 wherein said compound is selected from the group of 7β-phenylacetamido3-[3-(1,2,4-triazol-5-ylthio)-prop-1-(t)-enyl]-ceph-3-em-4-carboxylic acid and pharmaceutically acceptable salts thereof. 
     
     
       19. The compound of claim 16 wherein said compound is selected from the group of 7β-(α-hydroxy-α-phenylacetamido)-3-[3-(1,2,4-triazol-5-ylthio)-prop-1-(t)-enyl]-ceph-3-em-4-carboxylic acid and pharmaceutically acceptable salts thereof. 
     
     
       20. The compound of claim 16 wherein said compound is selected from the group of 7β-(α-phenyl-α-sulfoacetamido)-3-[3-(1,2,4-triazol-5-ylthio)-prop-1-(t)-enyl]-ceph-3-em-4-carboxylic acid and pharmaceutically acceptable salts thereof. 
     
     
       21. The compound of claim 16 wherein said compound is selected from the group of 7β-(α-carboxy-α-phenylacetamido)-3-[3-(1,2,4-triazol-5-ylthio)-prop-1-(t)-enyl]-ceph-3-em-4-carboxylic acid and pharmaceutically acceptable salts thereof. 
     
     
       22. The compound of claim 7 wherein R 4  is hydroxy, sulfo or carboxy and is an optically active D isomer. 
     
     
       23. The compound of claim 1 wherein said compound is selected from the group having the formula: ##STR27## wherein R 1 , R 2  and X are as defined in claim 1, and pharmaceutically acceptable salts thereof. 
     
     
       24. The compound of claim 23 wherein R 2  is diphenylmethyl. 
     
     
       25. The compound of claim 23 wherein R 2  is hydrogen and pharmaceutically acceptable salts thereof. 
     
     
       26. The compound of claim 25 wherein said compound is selected from the group of 3-[3-(1-methyltetrazol-5-ylthio)-prop-1-(t)-enyl]-7β-(α-amino-.alpha.-phenylacetamido)-ceph-3-em-4-carboxylic acid and pharmaceutically acceptable salts thereof. 
     
     
       27. The compound of claim 25 wherein said compound is selected from the group of 7β-(α-amino-α-p-hydroxyphenylacetamido)-3-[3-(1-methyltetrazol-5-ylthio)-prop-1-(t)-enyl]-ceph-3-em-4-carboxylic acid and pharmaceutically acceptable salts thereof. 
     
     
       28. The compound of claim 25 wherein said compound is selected from the group of 7β-(α-amino-α-phenylacetamido)-3-[3-(1,2,4-triazol-5-ylthio)-prop-1-(t)-enyl]-ceph-3-em-4-carboxylic acid and pharmaceutically acceptable salts thereof. 
     
     
       29. The compound of claim 25 wherein said compound is selected from the group of 7β-(α-amino-α-p-hydroxyphenylacetamido)-3-[3-(1,2,4-triazol-5-ylthio)-prop-1-(t)-enyl]-ceph-3-em-4-carboxylic acid and pharmaceutically acceptable salts thereof. 
     
     
       30. The compound of claim 23 wherein said compound is an optically active (D)-α-amino isomer. 
     
     
       31. The compound of claim 1 wherein said compound is selected from the group consisting of 7β-D-(α-hydroxy-α-phenylacetamido)-3-[3-(1-methyltetrazol-5-ylthio)-prop-1-(t)-enyl]-ceph-3-em-4-carboxylic acid;   7β-D-(α-amino-α-phenylacetamido)-3-[3-(1-methyltetrazol-5-ylthio)-prop-1-(t)-enyl]-ceph-3-em-4-carboxylic acid;   7β-D-(α-amino-α-p-hydroxyphenylacetamido)-3-[3-(1-methyltetrazol-5-ylthio)-prop-1-(t)-enyl]-ceph-3-em-4-carboxylic acid; and pharmaceutically acceptable salts thereof.     
     
     
       32. A compound having the formula: ##STR28## wherein the propenyl double bond is trans; R 1  is 1-methyltetrazol-5-yl or 1,2,4-triazol-5-yl; and R 2'   is diphenylmethyl, p-methoxy-benzyl, p-nitrobenzyl, o-nitrobenzyl, benzyl, t-butyl, 2,2,2-trichloroethyl, phenacyl or pivaloyloxymethyl. 
     
     
       33. A process for preparing the compounds of claim 32 which comprises reacting the corresponding 3-(1-hydroxyprop-2-enyl)-7β-(thiophen-2-yl-acetamido)-ceph-2-em-4-carboxylate ester with 5-mercapto-1-methyltetrazole or 5-mercapto-1,2,4-triazole to yield the corresponding compound of claim 41. 
     
     
       34. A process for preparing the compounds of claim 2 which comprises rearranging the C-2(3) double bond of the corresponding 3-[3-(1-methyltetrazol- or 1,2,4-triazol-5-ylthio)-prop-1-(t)-enyl]-7β-(thiophen-2-yl-acetamido)-ceph-2-em-4-carboxylate to the C-3(4) position via base catalysis or via oxidation and then cleaving the 7β-thiophen-2-yl-acetamido group thereby yielding the corresponding compound of claim 2. 
     
     
       35. A process for preparing the compounds of claim 1 of formulas III and IV, and optionally pharmaceutically acceptable salts thereof which comprises acylating the 7β-amino group and hydrolyzing the C-4-carboxylate ester of the corresponding 7β-amino-3-[3-(1-methyltetrazol- or 1,2,4-triazol-5-ylthio)-prop-1-(t)-enyl]-ceph-3-em-4-carboxylate ester to yield the corresponding compound of formulas III and IV and optionally reacting this product with a pharmaceutically acceptable cation to obtain the corresponding salt. 
     
     
       36. A composition for inhibiting the growth of bacteria comprising an effective amount of a compound of claim 7 in admixture with a compatible carrier. 
     
     
       37. A composition for inhibiting the growth of bacteria comprising an effective amount of a compound of claim 23 in admixture with a compatible carrier. 
     
     
       38. A composition of claim 36 for pharmaceutical use wherein the carrier is a pharmaceutically acceptable carrier. 
     
     
       39. A composition of claim 37 for pharmaceutical use wherein the carrier is a pharmaceutically accceptable carrier.

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